This invention relates to the preparation of a sterile article made from a polymer having a halogen-containing repeating unit, where the polymer contains a compound based on a poly(oxyalkylene) (POA). In particular, it relates reducing the yellowing of an article made from polyvinyl chloride (PVC) after exposure to gamma radiation by incorporating compounds based on poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) into the PVC.
PVC is a versatile thermoplastic that is widely used for making medical articles and for food packaging due to its clarity, gloss, unique versatility, excellent functional performance, inertness to fluids, and relatively low cost. Medical devices and food packaging are usually sterilized before they are used. While ethylene oxide sterilization imposes little or no harmful effects on the physical properties of PVC, radiation sterilization, such as with gamma rays, can adversely effect the polymer, such as yellowing it.
PEG, PEG dibenzoate, and PPG dibenzoate have been used as PVC plasticizers. They are primarily used as alternatives for phthlate plasticizers, such as dioctyl phthalate (DOP). The use of these materials may also improve other properties of PVC. (J. H. Lee, K. O. Kim, Y. M. Ju J. Biomed. Mater. Res (Appl. Biomater) 48, pages 328 to 334 (1999); W. D. Arendt, J. Lang J. Vinyl and Additive Technology, 4(3), pages 184 to 188 (1998); W. D. Arendt Plast. Eng. 35(9), pages 46 to 49 (1979); W. D. Arendt Plast. Eng. 25, pages 410 to 412 (1979).
We have discovered that POA-based compounds inhibit the yellowing of polymers having halogen-containing repeating units after exposure to sterilizing radiation. The stabilizers of this invention also improve the mechanical strength of PVC compounds and reduce or eliminate the need to use DOP.
Some of the stabilizers of this invention are novel compounds while others are commercially available.
The stabilizers of this invention have the general formula: TGOTxe2x80x2, where each T is independently selected from Rxe2x80x94, Rxe2x80x94COxe2x80x94, xe2x80x94P(R)2, xe2x80x94P(OR)2, xe2x80x94Si(R)3, or xe2x80x94Si(OR)3, Txe2x80x2 is T or A[GOT]n, each A is independently selected from LSxe2x80x94Sn(R)3xe2x88x92q(SLJ)q, Lxe2x80x94Oxe2x80x94Sn(R)xe2x88x92q(OLJ)q, (CH2)pSxe2x80x94Sn(R)3xe2x88x92q(S(CH2)pxe2x80x94J)q, LCO2Sn(R)3xe2x88x92q(OLCOxe2x80x94J)q, or LSn(Y)3xe2x88x92q(LJ)q when n is 0, from CO, E, COxe2x80x94Exe2x80x94CO, Si(R)2, Si(OR)2, (Si(R)2G)r, (COxe2x80x94Exe2x80x94COxe2x80x94G)r, (COxe2x80x94G)r, or (Exe2x80x94G)r when n is 1, and from P, PO, and trimellitate when n is 2, Y is xe2x80x94SLJ, xe2x80x94SLOR, xe2x80x94OLJ, xe2x80x94OLR, xe2x80x94S(CH2)pxe2x80x94J, xe2x80x94S(CH2)pR, OLCOxe2x80x94J, or OLCOOR, G is (Oxe2x80x94CH2xe2x80x94Rxe2x80x2CH)m, J is Oxe2x80x94(CH2CRxe2x80x2HO)T, L is CO(CH2)p, each R is independently selected from Rxe2x80x2, aralkyl from C6 to C12, and alkaryl from C6 to C12, each Rxe2x80x2 is independently selected from hydrogen, alkyl from C1 to C12, and aryl from C6 to C12, E is alkylene from C1 to C12, aralkylene from C6 to C12, alkarylene from C6 to C12, arylene from C6 to C12, m is 1 to 20, n is 0 to 2, p is 0 to 10, q is 0 to 3, and r is 1 to 20. The ethers (T=R, Txe2x80x2=R) are preferred and R is preferably alkyl from C1 to C8 as those stabilizers are more effective, Rxe2x80x2 is preferably methyl or phenyl because they increase the lipophilicity of the stabilizers, resulting in better miscibility with the polymers. The A group is preferably COxe2x80x94Exe2x80x94CO or (COxe2x80x94Exe2x80x94COxe2x80x94G)r because the lipophilicity of the materials can be tailored and these materials are easily prepared. The Y group is preferably xe2x80x94SLJ, xe2x80x94SLOR, xe2x80x94S(CH2)pxe2x80x94J, or xe2x80x94S(CH2)pR because they are more effective. Of the tin stabilizers, sulfer-containing tin stabilizers are preferred, because they are better thermo stabilizers. Finally, m is preferably 2 to 5 as smaller values may be less effective and greater values may not be compatible with PVC, resulting in a hazy appearance, n is preferably 0 to 1 because these stabilizers can better inhibit the discoloration of the polymers, p is preferably 1 to 2 because these stabilizers are readily available, q is preferably 1 to 2 because those stabilizers are also better thermal stabilizers, and r is preferably 2 to 5 because they mix well with PVC. Preferably, all the T groups are identical as those stabilizers are easier to prepare.
The general formula includes PEG and PPG ethers: Rxe2x80x94G xe2x80x94OR, PEG and PPG esters: Rxe2x80x94COxe2x80x94Gxe2x80x94OCOxe2x80x94R, tin compounds: (R)qSnxe2x80x94(MRxe2x80x3xe2x80x94Gxe2x80x94OT)4xe2x88x92q, silicates: (R)3xe2x80x94Sixe2x80x94Gxe2x80x94Si(R)3, phosphites: Pxe2x80x94(GOT)3, phosphates: OPxe2x80x94(GOT)3, phthalates: 
and trimellitates:
where M is O or S (and is preferably S) and Rxe2x80x3 is (CH2)pCOxe2x80x94, COxe2x80x94(CH3)pCOxe2x80x94, xe2x80x94(CH2)p, or xe2x80x94CO(CH2)pxe2x80x94 (and is preferably (CH2)pCOxe2x80x94).
Examples of PEG, PPG, and their ethers and esters include tri(propylene glycol), poly(propylene glycol), poly(propylene glycol)diglycidyl ether, dibutoxypropoxypropyl adipate, poly(propylene glycol di(2-ethylhexanoate), poly(propylene glycol) dibenzoate, di(propylene glycol) dibenzoate, poly(ethylene glycol) dibenzoate, and di(ethylene glycol) dibenzoate. Examples of tin compounds include dibutyltin bis(diethylene glycol monomethyl ether thioglycolate), dibutyltin bis(triethylene glycol monomethyl ether thioglycolate), dibutyltin bis(diethylene glycol monoethyl ether thioglycolate), dibutyltin bis(triethylene glycol monoethyl ether thioglycolate), dibutyltin bis(dipropylene glycol monoethyl ether thioglycolate), dibutyltin bis(tripropylene glycol monoethyl ether thioglycolate), bis(xcex2-carbomethoxyethoxyethoxy)tin bis(isooctylthioglycoate), bis(xcex2-carboethoxyethoxyethoxy)tin bis(isooctylthioglycoate), and bis(xcex2-carboethoxyethoxyethoxyethoxy)tin bis(isooctylthioglycoate). Examples of silicates include poly(propylene glycol) bistrimethylsily ether, poly(propylene glycol) bistrimethoxysily ether, poly(ethylene glycol) bistrimethylsily ether, and poly(ethylene glycol) bistrimethoxysily ether. Examples of phosphites include tri(methoxyethoxyethyl) phosphite, tri(ethoxyethoxyethyl) phosphite, tri(methoxypropoxypropyl) phosphite, tri(ethoxypropoxypropyl) phosphite, tri(methoxyethoxyethoxyethyl) phosphite, tri(ethoxyethoxyethoxyethyl) phosphite, tri(methoxypropoxypropbxypropyl) phosphite, and tri(ethoxypropoxypropoxypropyl) phosphite. Examples of phosphates include tri(methoxypropoxypropyl) phosphate, tri(ethoxypropoxypropyl) phosphate, tri(methoxyethoxyethoxyethyl) phosphate, tri(ethoxyethoxyethoxyethyl) phosphate, tri(methoxypropoxypropoxypropyl) phosphate, and tri(ethoxypropoxypropoxypropyl) phosphate. Examples of phthalates include di(diethylene glycol monomethyl ether) phthalate, di(triethylene glycol monomethyl ether) phthalate, di(diethylene glycol monoethyl ether) phthalate, di(triethylene glycol monoethyl ether) phthalate, di(dipropylene glycol monoethyl ether) phthalate, and di(tripropylene glycol monoethyl ether) phthalate. Examples of trimellitates include tri(diethylene glycol monomethyl ether) trimellitate, di(triethylene glycol monomethyl ether) trimellitate, di(diethylene glycol monoethyl ether) trimellitate, di(triethylene glycol monoethyl ether) trimellitate, di(dipropylene glycol monoethyl ether) trimellitate, and di(tripropylene glycol monoethyl ether) trimellitate. The preferred stabilizers are ethers and esters of PEG and PPG because many are commercially available.
Polyethylene glycol and polypropylene glycol ethers and esters that are not commercially available are easily made by, for example, condensing polyethylene glycol or polypropylene glycol with an alcohol (to make an ether) or with an acid chloride (to make an ester), as is well-known in the art. Of the above compounds, the PEG and PPG ethers, silyl ethers, and esters are well known. Phthalates such as dimethyl glycol phthalate, diethyl glycol phthalate, dibutyl glycol phthalate; di-2-(2-methoxyethoxy)ethyl phthalate; di-2-(2-ethoxyethoxy)ethyl phthalate; di-2-(2-butoxyethoxy)ethyl phthalate; di-2-(2-hexyloxyethoxy)ethyl phthalate; bis[2-[2-(2-ethoxyethoxy)ethoxy]ethyl] phthalate are also known. The known trimellitates include tris(2-methoxyethyl)trimellitates, and tris[2-(2-methoxyethoxy)ethyl]trimellitates; the known phosphorous compounds include tris(2-methoxyethyl)phosphite, tris[2-(2-methoxyethoxy)ethyl]phosphite, tris(2-methoxyethyl)phosphate, tris[2-(2-methoxyethoxy)ethyl]phosphate, tris[2-[2-(2-methoxyethoxy)ethoxy]ethyl] phosphate. The tin compounds, some of the phosphites, phosphates, phthalates, and trimellitates are believed to be novel compounds. In particular, compounds having the general formula (R)qSnxe2x80x94(MRxe2x80x3xe2x80x94OCH2xe2x80x94Rxe2x80x2CH]mxe2x80x94OT)4xe2x88x92q, Pxe2x80x94[(OCH2xe2x80x94Rxe2x80x2CH)mxe2x80x94OT]3, 
where each Rxe2x80x2 is independently selected from alkyl from C1 to C12, and aryl from C6 to C12, and R, M, T, m, and q are the same as hereinabove defined, are believed to be novel. They can be made by, for example, reacting PCl3 with methyl monoethers of PEG or PPG. Stabilizers containing an (COxe2x80x94Exe2x80x94COxe2x80x94G)r, (COxe2x80x94G)r, (Exe2x80x94G)r, or (Si(R)2G)r group are polymers made by reacting a difunctional acid, acid chloride, or anhydride, such as phosgene, adipic acid, malonic anhydride, or dichlorosilane with a PEG or a PPG.
The stabilizers of this invention are effective against the oxidation of haloginated polymers such as PVC, poly(vinylidene chloride), chlorinated polyethylene, and chlorinated polypropylene. The preferred polymer is PVC because PVC is more frequently used in medical applications where it is subjected to gamma radiation.
The polymer can be stabilized by the addition of about 0.005 to about 65 phr (parts by weight per 100 part by weight of the polymer) of the stabilizer to the polymer. Less stabilizer is less effective and more stabilizer offers little additional benefit; the preferred amount of stabilizer is about 0.2 to about 20 phr. The stabilizer can be added to the polymer in a variety of ways, such as by mixing the reactants at the beginning or during polymerization. The stabilizer is preferably added after at least 70 wt % of the monomer has polymerized. The stabilizer can be added as a solid or with a solvent as a slurry or a solution. Common organic solvents can be used, such as N-methylpyrrolidone, diglyme, acetamide, acetone, methanol, ethanol, isopropanol, dimethylsulfoxide, or dimethylformamide; water can also be used. Water miscible solvents, such as acetone, tetrahydrofuran, and methanol, are preferred for PVC. If the stabilizer is a solid, it is preferable to add the stabilizer in a solvent as that achieves a more uniform distribution of the stabilizer in the polymer. The stabilizer can also be added along with shortstop, or during the drying or compounding of the polymer. Various methods can be used for compounding, including milling, dry mixing, and extrusion. The stabilizers function as antioxidants to inhibit various forms of oxidation.